Original Articles
Copyright ©The Author(s) 2000. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 15, 2000; 6(5): 688-692
Published online Oct 15, 2000. doi: 10.3748/wjg.v6.i5.688
Effect of hepatocyte apoptosis induced by TNF-α on acute severe hepatitis in mouse models
Guo Qing Zang, Xia Qiu Zhou, Hong Yu, Qing Xie, Guo Ming Zhao, Bin Wang, Qing Guo, Yue Qin Xiang, Dan Liao
Guo Qing Zang, Xia Qiu Zhou, Hong Yu, Qing Xie, Guo Ming Zhao, Bin Wang, Qing Guo, Yue Qin Xiang, Dan Liao, Department of Infectious Diseases, Rujin Hospital, Shanghai Second Medical University, Shanghai 200025, China
Guo Qing Zang, graduated from Xian Medical University as a postgraduate in 1990, associate professor of lemology, engaged in diagnosis and treatment of viral hepatitis and hemorrahgic fever with renal syndrome, having 12 papers published.
Author contributions: All authors contributed equally to the work.
Correspondence to: Dr. Guo Qing Zang, Department of Infectious Diseases, Rujin Hospital, Shanghai Second Medical University, Shanghai 200025, China
Telephone: 0086-21-64311242
Received: April 3, 2000
Revised: May 9, 2000
Accepted: May 16, 2000
Published online: October 15, 2000
Abstract

AIM: To study the effect of hepatocyte apoptosis and necrosis induced by TNF-α on the pathogenesis of acute severe hepatitis (ASH).

METHODS: The model of ASH was prepared in D-galactosamine (GalN) sensitized BALB/c mice by injection of either endotoxin (ET) or tumor necrosis factor-α (TNF-α). Morphological changes of apoptotic hepatocytes were studied by both light and electron microscope and in site end labeling method (ISEL). Molecular biological changes of DNA ladder were observed by electrophoresis of extract from liver tissues. Biochemical changes were measured by alanine aminotransferase (ALT), aspartic aminotransferase (AST) and TNF-α. The relation between apoptosis and necrosis was evaluated simultaneously.

RESULTS: The sequence of hepatocyte apoptosis, necrosis, and final death from ASH was observed both in GalN/ET and GalN/TNF-α group. Apoptosis was prominent at 3.5 h and 6 h after injection of inducer, while necrosis became dominant at 9 h after challenge. The appearance of apoptosis was earlier in GalN/TNF-α group than that in GalN/ET group. Pretreatment of mice with antiTNF IgG1 may completely prevent the liver injury induced by GalN/ET.

CONCLUSION: TNF-α can cause liver damage by inducing hepatic apoptosis and necrosis in mice with endotoxemia.

Keywords: tumor necrosis factor; hepatitis; apoptosis; alanine transaminase; aspartate transaminase; endotoxins; mice